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. 1995 Nov;37(5):684–689. doi: 10.1136/gut.37.5.684

Kinetic studies on colonocyte metabolism of short chain fatty acids and glucose in ulcerative colitis.

M R Clausen 1, P B Mortensen 1
PMCID: PMC1382875  PMID: 8549946

Abstract

Short chain fatty acids (SCFAs) are potentially valuable as a topical therapy for distal ulcerative colitis. The mechanism of action is unknown but may involve improved intracellular energy production as previous evidence indicates that colonocyte oxidation of butyrate is impaired in ulcerative colitis. No information is, however, available on human mucosal metabolism of acetate and propionate in either health or disease or the Vmax and Km values of butyrate oxidation. The aim of the study was to assess the kinetic parameters, Vmax and Km, of the complete oxidation of short chain fatty acids and glucose by human colonocytes and to explore whether a metabolic abnormality could be confirmed in patients with ulcerative colitis. Colonocytes were isolated from surgical specimens obtained from 14 patients with ulcerative colitis and eight control subjects. Incubations were performed in the presence of a concentration range of 14C-labelled acetate, propionate butyrate, and glucose. Oxidation rates were obtained by quantifying the production of 14CO2. Vmax and Km were calculated by computer fitting of the data to a Michaelis-Menten plot. No significant differences were shown in either Vmax or Km values of any of the SCFAs or glucose comparing controls and patients with ulcerative colitis. Comparing the results obtained regarding the individual SCFAs, the most striking difference was the considerably lower Km value of butyrate. The apparent Vmax of acetate tended to be higher than Vmax of propionate and butyrate. Vmax of glucose oxidation was significantly lower compared with the Vmax values of SCFA oxidation. The study shows the ability of isolated human colonocytes to utilise each of the three major SCFAs, but does not support a pathogenic role for defective metabolism of butyrate in ulcerative colitis. The considerably lower Km of butyrate oxidation supports a specific role of butyrate as an energy source for the colonic mucosa in both health and ulcerative colitis.

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Selected References

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  1. Breuer R. I., Buto S. K., Christ M. L., Bean J., Vernia P., Paoluzi P., Di Paolo M. C., Caprilli R. Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report. Dig Dis Sci. 1991 Feb;36(2):185–187. doi: 10.1007/BF01300754. [DOI] [PubMed] [Google Scholar]
  2. Chapman M. A., Grahn M. F., Boyle M. A., Hutton M., Rogers J., Williams N. S. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis. Gut. 1994 Jan;35(1):73–76. doi: 10.1136/gut.35.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clausen M. R., Mortensen P. B. Kinetic studies on the metabolism of short-chain fatty acids and glucose by isolated rat colonocytes. Gastroenterology. 1994 Feb;106(2):423–432. doi: 10.1016/0016-5085(94)90601-7. [DOI] [PubMed] [Google Scholar]
  4. Cummings J. H., Macfarlane G. T. The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol. 1991 Jun;70(6):443–459. doi: 10.1111/j.1365-2672.1991.tb02739.x. [DOI] [PubMed] [Google Scholar]
  5. Cummings J. H., Pomare E. W., Branch W. J., Naylor C. P., Macfarlane G. T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987 Oct;28(10):1221–1227. doi: 10.1136/gut.28.10.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dankert J., Zijlstra J. B., Wolthers B. G. Volatile fatty acids in human peripheral and portal blood: quantitative determination vacuum distillation and gas chromatography. Clin Chim Acta. 1981 Mar 5;110(2-3):301–307. doi: 10.1016/0009-8981(81)90359-4. [DOI] [PubMed] [Google Scholar]
  7. Finnie I. A., Taylor B. A., Rhodes J. M. Ileal and colonic epithelial metabolism in quiescent ulcerative colitis: increased glutamine metabolism in distal colon but no defect in butyrate metabolism. Gut. 1993 Nov;34(11):1552–1558. doi: 10.1136/gut.34.11.1552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gamet L., Daviaud D., Denis-Pouxviel C., Remesy C., Murat J. C. Effects of short-chain fatty acids on growth and differentiation of the human colon-cancer cell line HT29. Int J Cancer. 1992 Sep 9;52(2):286–289. doi: 10.1002/ijc.2910520222. [DOI] [PubMed] [Google Scholar]
  9. Holtug K., Rasmussen H. S., Mortensen P. B. Short chain fatty acids in inflammatory bowel disease. The effect of bacterial fermentation of blood. Scand J Clin Lab Invest. 1988 Nov;48(7):667–671. [PubMed] [Google Scholar]
  10. Hove H., Mortensen P. B. Influence of intestinal inflammation (IBD) and small and large bowel length on fecal short-chain fatty acids and lactate. Dig Dis Sci. 1995 Jun;40(6):1372–1380. doi: 10.1007/BF02065554. [DOI] [PubMed] [Google Scholar]
  11. McNeil N. I., Cummings J. H., James W. P. Short chain fatty acid absorption by the human large intestine. Gut. 1978 Sep;19(9):819–822. doi: 10.1136/gut.19.9.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Morita A., Tsao D., Kim Y. S. Effect of sodium butyrate on alkaline phosphatase in HRT-18, a human rectal cancer cell line. Cancer Res. 1982 Nov;42(11):4540–4545. [PubMed] [Google Scholar]
  13. Mortensen P. B., Hove H., Clausen M. R., Holtug K. Fermentation to short-chain fatty acids and lactate in human faecal batch cultures. Intra- and inter-individual variations versus variations caused by changes in fermented saccharides. Scand J Gastroenterol. 1991 Dec;26(12):1285–1294. doi: 10.3109/00365529108998626. [DOI] [PubMed] [Google Scholar]
  14. Peters S. G., Pomare E. W., Fisher C. A. Portal and peripheral blood short chain fatty acid concentrations after caecal lactulose instillation at surgery. Gut. 1992 Sep;33(9):1249–1252. doi: 10.1136/gut.33.9.1249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Roediger W. E., Duncan A., Kapaniris O., Millard S. Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis. Gastroenterology. 1993 Mar;104(3):802–809. doi: 10.1016/0016-5085(93)91016-b. [DOI] [PubMed] [Google Scholar]
  16. Roediger W. E., Heyworth M., Willoughby P., Piris J., Moore A., Truelove S. C. Luminal ions and short chain fatty acids as markers of functional activity of the mucosa in ulcerative colitis. J Clin Pathol. 1982 Mar;35(3):323–326. doi: 10.1136/jcp.35.3.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Roediger W. E., Nance S. Selective reduction of fatty acid oxidation in colonocytes: correlation with ulcerative colitis. Lipids. 1990 Oct;25(10):646–652. doi: 10.1007/BF02536016. [DOI] [PubMed] [Google Scholar]
  18. Roediger W. E. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut. 1980 Sep;21(9):793–798. doi: 10.1136/gut.21.9.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Roediger W. E. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet. 1980 Oct 4;2(8197):712–715. doi: 10.1016/s0140-6736(80)91934-0. [DOI] [PubMed] [Google Scholar]
  20. Roediger W. E., Truelove S. C. Method of preparing isolated colonic epithelial cells (colonocytes) for metabolic studies. Gut. 1979 Jun;20(6):484–488. doi: 10.1136/gut.20.6.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rubinstein R., Howard A. V., Wrong O. M. In vivo dialysis of faeces as a method of stool analysis. IV. The organic anion component. Clin Sci. 1969 Oct;37(2):549–564. [PubMed] [Google Scholar]
  22. Ruppin H., Bar-Meir S., Soergel K. H., Wood C. M., Schmitt M. G., Jr Absorption of short-chain fatty acids by the colon. Gastroenterology. 1980 Jun;78(6):1500–1507. [PubMed] [Google Scholar]
  23. Scheppach W., Sommer H., Kirchner T., Paganelli G. M., Bartram P., Christl S., Richter F., Dusel G., Kasper H. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology. 1992 Jul;103(1):51–56. doi: 10.1016/0016-5085(92)91094-k. [DOI] [PubMed] [Google Scholar]
  24. Senagore A. J., MacKeigan J. M., Scheider M., Ebrom J. S. Short-chain fatty acid enemas: a cost-effective alternative in the treatment of nonspecific proctosigmoiditis. Dis Colon Rectum. 1992 Oct;35(10):923–927. doi: 10.1007/BF02253492. [DOI] [PubMed] [Google Scholar]
  25. Steinhart A. H., Brzezinski A., Baker J. P. Treatment of refractory ulcerative proctosigmoiditis with butyrate enemas. Am J Gastroenterol. 1994 Feb;89(2):179–183. [PubMed] [Google Scholar]
  26. Vernia P., Caprilli R., Latella G., Barbetti F., Magliocca F. M., Cittadini M. Fecal lactate and ulcerative colitis. Gastroenterology. 1988 Dec;95(6):1564–1568. doi: 10.1016/s0016-5085(88)80078-7. [DOI] [PubMed] [Google Scholar]
  27. Vernia P., Gnaedinger A., Hauck W., Breuer R. I. Organic anions and the diarrhea of inflammatory bowel disease. Dig Dis Sci. 1988 Nov;33(11):1353–1358. doi: 10.1007/BF01536987. [DOI] [PubMed] [Google Scholar]

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